Epidemiological studies have identified dietary zinc deficiency methylbenzylnitrosamine (MBN) and ethanol as factors which appear to be associated with an increased incidence of esophageal carcinoma in man. Animal models have confirmed that dietary zinc deficiency and chronic consumption of ethanol increase the incidence of NMBA-induced esophageal carcinoma. The proposed mechanism of nitrosamine induced carcinogenesis is viewed as a complex process involving metabolic activation of the carcinogen, detoxification of activated metabolites, chemical modification of cellular constituants, including DNA, and repair of critical cellular damage. Nitrosamines methylate DNA forming O6 methylguanine adducts. It is proposed that these adducts lead to misreading of the DNA, and induce alterations in the genetic information which lead to cancer. The postulated mechanism of MBN induced esophageal carcinoma is through oxidation of MBN to form benzaldehyde, and a carbonium ion which methylates DNA. Our previous studies examined the role of dietary zinc deficiency on the first step in this schema. We demonstrated a tenfold increase in the cytochrome P-450 dependent esophageal microsomal metabolism of MBN, in the zinc deficient rat. The mechanism of this increase in metabolism, as well as the effects of zinc deficiency and ethanol on the other aspects of MBN-induced esophageal carcinoma remain to be determined. This study will further examine the role of zinc and ethanol in the esophageal microsomal metabolism of MBN and examine the formation and repair of O6 methylguanine in the DNA of zinc deficient and control rat esophagi treated with MBN. A better understanding of the mechanisms by which dietary factors increase the incidence of esophageal carcinoma may assist in the prevention and treatment of human carcinoma.